Date of Award

2018

Document Type

Honors Thesis (Open Access)

Department

Colby College. Biology Dept.

Advisor(s)

Syed Tariq Ahmad

Second Advisor

Melissa J. Glenn

Abstract

Schizophrenia is a chronic disorder characterized by three symptom categories: positive (hallucinations, delusions), negative (anhedonia, anxiety), and cognitive (sensory processing and memory deficits). We worked with a biallelic deletion of the Disrupted-in-schizophrenia-1 (DISC1) gene in Sprague-Dawley rats to facilitate our understanding of the biological bases of schizophrenia. Mutations of DISC1 are associated with a higher prevalence of schizophrenia. Adult DISC1 knockout, compared to wildtype, rats display features of schizophrenia-like outcomes in rodent models. The present study investigated the progression of the cognitive symptom deficits in prepulse inhibition (PPI), assessing animals at postnatal days 17 (pre-weaning), 26 (post-weaning), 39 (adolescent), and 67 (adult). Cohorts of untested rats were sacrificed at each time to investigate the loss of GABAergic, parvalbumin-containing interneurons which occurs in schizophrenia. Also under examination was the extent to which the emergence and severity of these impairments were different between males and females; schizophrenia onset and symptoms can be sexually dimorphic.The findings were that males DISC1 knockout rats displayed enhanced PPI at the pre-weaning timepoint and impaired at the adult timepoint. Females exhibited little evidence of PPI deficits. We also performed a two-hit model with adult females finding that an acute dose of amphetamine could induce deficits in knockout, but not wildtype rats. Additionally, in a cohort of adult animals, male DISC1 knockouts revealed deficits in dendritic complexity while females did not. These findings highlight the importance of including females in the study of schizophrenia.

Keywords

schizophrenia, sex differences, development

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